New insights into immunoporosis: the impact of ovariectomy on immune cell population in lymph nodes and spleen.

It is increasingly appreciated that the immune cells and inflammatory mediators contribute to the impaired osteogenic potential under osteoporotic conditions. Previous studies in experimental animals focused on immune cells isolated from blood or bone marrow. Here we highlight the importance of unraveling the interactions between peripheral tissues, such as spleen and lymph nodes, and bone morphologic markers. Ovariectomized (OVX) animals underwent bilateral ovariectomy at the age of 9 mo. Four, 8, and 12 wk after ovariectomy, osteoporotic parameters and the immunoprofile were investigated by flow cytometric analysis of blood, lymph node, and spleen paired with immunohistochemistry. Ex vivo high-resolution micro-computed tomography (micro-CT) and hard tissue histology were performed on the excised tibiae. We observed trabecular bone loss, with corresponding decreases in bone volume to tissue volume (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D), as well as an increase in trabecular separation (Tb.Sp) in the OVX rats after 12 wk. Quantitative FACS analysis revealed significantly decreased percentage of granulocytes in lymph nodes at 12 wk in OVX. Correlation of distinct immune cell populations to bone morphologic markers showed that the percentage of granulocytes positively correlated with the Tb.N and Conn.Dn and negatively with the Tb.Sp both in the lymph nodes and in the spleen at 8 wk. At 12 wk after ovariectomy, however, the percentage of granulocytes correlated negatively with BV/TV, Tb.Th, and Tb. N. There was no correlation between distinct immune cells in the blood and bone morphologic markers. Hence, the presented data highlight the unmet need to investigate other compartments rather than blood and bone marrow.NEW & NOTEWORTHY There is supporting immunological evidence in the development of osteoporosis highlighted by bone alterations. Measurements of immune cells in the blood and bone marrow do not always reflect the multifactorial, pathologic situation linked to osteoporosis. Here, we pinpoint to distinct immune cell populations in peripheral tissues, especially in lymph nodes, which are affected during the onset of osteoporosis.